IMPORTANCE: Observational studies have reported that statin use may be associated with improved outcomes of various infections. Ventilator-associated pneumonia (VAP) is the most common infection in the intensive care unit (ICU) and is associated with substantial mortality. OBJECTIVE: To determine whether statin therapy can decrease day-28 mortality in patients with VAP. DESIGN, SETTING, AND PARTICIPANTS: Randomized, placebo-controlled, double-blind, parallelgroup, multicenter trial performed in 26 intensive care units in France from January 2010to March 2013. For power to detect an 8%absolute reduction in the day-28 mortality rate,we planned to enroll 1002 patients requiring invasive mechanical ventilation for more than 2 days and having suspected VAP, defined as a modified Clinical Pulmonary Infection Score of 5 or greater. The futility stopping ruleswere an absolute increase in day-28 mortality of at least 2.7% with simvastatin compared with placebo after enrollment of the first 251 patients. INTERVENTIONS: Participants were randomized to receive simvastatin (60mg) or placebo, started on the same day as antibiotic therapy and given until ICU discharge, death, or day 28, whichever occurred first. MAIN OUTCOMES AND MEASURES: Primary outcomewas day-28 mortality. Day-14, ICU, and hospital mortality rates were determined, as well as duration of mechanical ventilation and Sequential Organ Failure Assessment (SOFA) scores on days 3, 7, and 14. RESULTS: The study was stopped for futility at the first scheduled interim analysis after enrollment of 300 patients, of whom all but 7% in the simvastatin group and 11% in the placebo group were naive to statin therapy at ICU admission. Day-28 mortality was not lower in the simvastatin group (21.2% [95% CI, 15.4% to 28.6%) than in the placebo group (15.2% [95% CI, 10.2% to 22.1%]; P = .10; hazard ratio, 1.45 [95% CI, 0.83 to 2.51]); the between-group difference was 6.0% (95% CI, -3.0% to 14.9%). In statin-naive patients, day-28 mortality was 21.5% (95% CI, 15.4% to 29.1%) with simvastatin and 13.8% (95% CI, 8.8% to 21.0%) with placebo (P = .054) (between-group difference, 7.7% [95% CI, -1.8% to 16.8%). There were no significant differences regarding day-14, ICU, or hospital mortality rates; duration of mechanical ventilation; or changes in SOFA score. CONCLUSIONS AND RELEVANCE: In adults with suspected VAP, adjunctive simvastatin therapy compared with placebo did not improve day-28 survival. These findings do not support the use of statins with the goal of improving VAP outcomes. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01057758.

In mice, disseminated coagulation, inflammation, and ischemia induce neurological damage that can lead to death. These symptoms result from circulating bubbles generated by a pathogenic decompression. Acute fluoxetine treatment or the presence of the TREK-1 potassium channel increases the survival rate when mice are subjected to an experimental dive/decompression protocol. This is a paradox because fluoxetine is a blocker of TREK-1 channels. First, we studied the effects of an acute dose of fluoxetine (50 mg/kg) in wild-type (WT) and TREK-1 deficient mice (knockout homozygous KO and heterozygous HET). Then, we combined the same fluoxetine treatment with a 5-day treatment protocol with spadin, in order to specifically block TREK-1 activity (KO-like mice). KO and KO-like mice were regarded as antidepressed models. In total, 167 mice (45 WTcont 46 WTflux 30 HETflux and 46 KOflux) constituting the flux-pool and 113 supplementary mice (27 KO-like 24 WTflux2 24 KO-likeflux 21 WTcont2 17 WTno dive) constituting the spad-pool were included in this study. Only 7% of KO-TREK-1 treated with fluoxetine (KOflux) and 4% of mice treated with both spadin and fluoxetine (KO-likeflux) died from decompression sickness (DCS) symptoms. These values are much lower than those of WT control (62%) or KO-like mice (41%). After the decompression protocol, mice showed significant consumption of their circulating platelets and leukocytes. Spadin antidepressed mice were more likely to exhibit DCS. Nevertheless, mice which had both blocked TREK-1 channels and fluoxetine treatment were better protected against DCS. We conclude that the protective effect of such an acute dose of fluoxetine is enhanced when TREK-1 is inhibited. We confirmed that antidepressed models may have worse DCS outcomes, but concomitant fluoxetine treatment not only decreased DCS severity but increased the survival rate.

Central nervous system involvement by malignant cells is a rare complication of Waldenstrm macroglobulinemia, and this clinicopathological entity is referred to as the Bing-Neel syndrome. There is currently no consensus on the diagnostic criteria, therapeutic approaches and response evaluation for this syndrome. In this series, we retrospectively analyzed 44 French patients with Bing-Neel syndrome. Bing-Neel syndrome was the first manifestation of Waldenstrm macroglobulinemia in 36% of patients. When Waldenstrm macroglobulinemia was diagnosed prior to Bing-Neel syndrome, the median time interval between this diagnosis and the onset of Bing-Neel syndrome was 8.9 years. This study highlights the possibility of the occurrence of Bing-Neel syndrome without any other evidence of progression of Waldenstrm macroglobulinemia. The clinical presentation was heterogeneous without any specific signs or symptoms. Biologically, the median lymphocyte count in the cerebrospinal fluid was 31/mm(3). Magnetic resonance imaging revealed abnormalities in 78% of the cases. The overall response rate after first-line treatment was 70%, and the overall survival rate after the diagnosis of Bing-Neel syndrome was 71% at 5 years. Altogether, these results suggest that Bing-Neel syndrome should be considered in the context of any unexplained neurological symptoms associated with Waldenstrm macroglobulinemia. The diagnostic approach should be based on cerebrospinal fluid analysis and magnetic resonance imaging of the brain and spinal axis. It still remains difficult to establish treatment recommendations or prognostic factors in the absence of large-scale, prospective, observational studies.

Hematologic diseases are a significant part of health disorders in Benin. As an example, anemia is the second cause of hospitalization, measuring up to 7.9% all over the country (National Plan of Sanitary Development, 2009-2018). By contrast, there is only one active hematologist in the country. Thanks to two partnerships, on one hand between the health sciences faculty in Cotonou (Benin) and the medicine one in Tours (France), and on the other hand between the Beninese Blood Transfusion National Agency and the French Blood Establishment, a first blood transfusion and hematology formation was held in Cotonou on December 2014. Among other benefits, was created an hematology-transfusion network in order to facilitate relations between Beninese hospital doctors, with the support of the two French partner institutions. The article describes this progress.

The World Health Organization (WHO) has added detection of the JAK2 tyrosine kinase mutation, JAK2 V617F, in the diagnostic work up for myeloproliferative neoplasms (MPNs), especially for polycythemia vera (PV) and essential thrombocythemia (ET). The rational use of this new marker requires the determination of accurate thresholds of clinical significance and thus implies clarification of the presence or not of JAK2 V617F in healthy individuals. The aim of this study was to determine JAK2 V617F mutation levels in healthy subjects with no clinical or biological signs indicative of MPN. Results in 198 healthy subjects indicate that a very accurate quantification of JAK2 V617F is feasible when the analysis is performed with a highly sensitive and reliable RQ-PCR assay, and that the JAK2 V617F mutation may be detectable in very rare cases of healthy volunteers with no clinical symptoms of MPNs or blood disorder, but only at levels around the analytical threshold of the assay (0.035%) and far below the commonly accepted positivity cutoff (1%).

Plasmodium falciparum malaria is usually transmitted by mosquitoes. We report 2 cases in France transmitted by other modes: occupational blood exposure and blood transfusion. Even where malaria is not endemic, it should be considered as a cause of unexplained acute fever.